wortmannin has been researched along with myricetin* in 1 studies
1 other study(ies) available for wortmannin and myricetin
Article | Year |
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Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine.
The specific phosphoinositide 3-kinase (PI3K) inhibitors wortmannin and LY294002 have been invaluable tools for elucidating the roles of these enzymes in signal transduction pathways. The X-ray crystallographic structures of PI3Kgamma bound to these lipid kinase inhibitors and to the broad-spectrum protein kinase inhibitors quercetin, myricetin, and staurosporine reveal how these compounds fit into the ATP binding pocket. With a nanomolar IC50, wortmannin most closely fits and fills the active site and induces a conformational change in the catalytic domain. Surprisingly, LY294002 and the lead compound on which it was designed, quercetin, as well as the closely related flavonoid myricetin bind PI3K in remarkably different orientations that are related to each other by 180 degrees rotations. Staurosporine/PI3K interactions are reminiscent of low-affinity protein kinase/staurosporine complexes. These results provide a rich basis for development of isoform-specific PI3K inhibitors with therapeutic potential. Topics: Adenosine Triphosphate; Amino Acid Sequence; Androstadienes; Animals; Binding Sites; Brain; Cattle; Chromones; Crystallography, X-Ray; Enzyme Inhibitors; Flavonoids; Humans; Models, Molecular; Molecular Sequence Data; Morpholines; Peptide Fragments; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Protein Conformation; Protein Structure, Secondary; Quercetin; Recombinant Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Staurosporine; Wortmannin | 2000 |